Progress in the discovery of CC chemokine receptor 2 antagonists, 2009 - 2012.

INTRODUCTION: CC chemokine receptor 2 (CCR2) is a key mediator of the activation and migration of inflammatory monocytes. As such, it has been investigated extensively as a target for therapeutic intervention in a diverse range of diseases. AREAS COVERED: This article reviews both the patent and peer-reviewed literature on the discovery of CCR2 antagonists from January 2009 to December 2012. Developments have occurred within each of the major chemical families of CCR2 antagonists, and are framed in that context. As has been true historically, a number of the compound families also exhibit substantial activity against the related CC chemokine receptor 5 (CCR5), making them formally CCR2/5-dual antagonists. EXPERT OPINION: Significant progress continues to be made in identifying novel, potent CCR2 antagonists. In addition, researchers have had success in addressing issues related to selectivity, cardiac safety, and preclinical pharmacokinetics. Establishing proof-of-concept in clinical trials remains the primary challenge for the field.